Fungal
infections could cause tremendous decreases in crop yield
and quality. Natural products, including flavonoids and (iso)quinolines,
have always been an important source for lead discovery in medicinal
and agricultural chemistry. To promote the discovery and development
of new fungicides, a series of 3-(iso)quinolinyl-4-chromenone derivatives
was designed and synthesized by the active substructure splicing principle
and evaluated for their antifungal activities. The lead optimization
was guided by bioactivity. The bioassay data revealed that the 3-quinolinyl-4-chromenone 13 showed significant in vitro activities
against S. sclerotiorum, V. mali, and B. cinerea with EC50 values of 3.65, 2.61, and 2.32 mg/L, respectively.
The 3-isoquinolinyl-4-chromenone 25 exhibited excellent in vitro activity against S. sclerotiorum with an EC50 value of 1.94 mg/L, close to that of commercial
fungicide chlorothalonil (EC50 = 1.57 mg/L) but lower than
that of boscalid (EC50 = 0.67 mg/L). For V. mali and B. cinerea, 3-isoquinolinyl-4-chromenone 25 (EC50 =
1.56, 1.54 mg/L) showed significantly higher activities than chlorothalonil
(EC50 = 11.24, 2.92 mg/L). In addition, in vivo experiments proved that compounds 13 and 25 have excellent protective fungicidal activities with inhibitory
rates of 88.24 and 94.12%, respectively, against B.
cinerea at 50 mg/L, while the positive controls chlorothalonil
and boscalid showed inhibitory rates of 76.47 and 97.06%, respectively.
Physiological and biochemical studies showed that the primary action
of mechanism of compounds 13 and 25 on S. sclerotiorum and B. cinerea may involve changing mycelial morphology and increasing cell membrane
permeability. In addition, compound 13 may also affect
the respiratory metabolism of B. cinerea
. This study revealed that compounds 13 and 25 could be promising candidates for the development
of novel fungicides in crop protection.